Transmissible spongiform encephalopathies are a group of rapidly progressive, fatal, and untreatable neurodegenerative syndromes. Human transmissible spongiform encephalopathies include, e.g., classical Creutzfeldt-Jakob disease (CJD), which has sporadic, iatrogenic, and familial forms, and variant CJD (vCJD) (Will et al., Lancet 347:921-25, 1996; Collinge, Lancet 354:317-23, 1999; Cashman, Can. Med. Assoc. J. 157:1381-5, 1997; Coulthart & Cashman, Can. Med. Assoc. J. 165:51-8, 2001); and kuru. Scrapie affects sheep and goats. Additionally, mink, deer, elk, and bovines are affected by transmissible spongiform encephalopathy. Bovine Spongiform Encephalopathy (BSE) has been a major economic and animal welfare epizootic in Europe since 1986 and has been implicated as the causative agent of human vCJD.
Prions are infectious agents that are associated with the transmissible spongiform encephalopathies noted above. The prion diseases are characterized by spongiform change (e.g., microcavitation of the brain, usually predominant in gray matter), neuronal cell loss, astrocytic proliferation disproportionate to neuronal loss, and accumulation of an abnormal amyloidogenic protein, sometimes in discrete plaques in the brain.
TSEs are associated with accumulation of an abnormal form of a protein (PrPSc) naturally produced by the host, PrPc. PrPSc can accumulate in the brain and peripheral lymphoid system as amyloid plaques or deposits. PrPc expression occurs in cells of many other tissues and fluids in the body (e.g. blood leucocytes, heart) but no plaque deposits have yet been detected in TSEs.
Antibodies that are specific for an abnormal isoform of a prion protein are known in the art (Paramithiotis et al. 2003. Nature Medicine. 9:893-899). However, except for Schmerr et al. 1999. J. Chromatog. A 853: 207-214) there are no blood tests for TSEs available at present. Additionally, no simple tests for TSEs are available.
TSE infectivity has been demonstrated in the blood and leucocytes of sheep infected with scrapie and in bovine spongiform encelphalopathy (BSE). See, e.g., Hunter et al. 2002. J. Gen. Virol. 83:2897-2905). PrPSc has been demonstrated in leucocyte preparations of scrapie infected blood. See, e.g., Schmerr et al., 1999. J. Chromatog. A 853: 207-214.
The availability of methods that can distinguish PrPSc from PrPc would be of great value in development of a test for prion infection in blood or other tissues accessible to sampling. Accordingly, a need exists in the art for simple testing of samples for the presence of prions.